Urea Cycle : Definition, Function, Reaction And Diagnosis

Urea cycle

The Urea Cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2) 2CO from ammonia (NH3). This cycle occurs in ureotelic organisms. The urea cycle converts highly toxic ammonia into urea for immersion. This cycle was the first metabolic cycle to be discovered, five years ago by the discovery of the TCA cycle (Hans Krebs and Kurt Henseleit, 1932). The urea cycle is primarily in the liver and in the kidney, to some degree.

In humans and mammals, approximately 80% of nitrogen is produced in the form of urea emitted, which is produced through a series of reactions in cytosol and mitochondrial matrix of liver cells. These reactions are collectively called the urea cycle or the Krebs-Hensleit cycle.

Ammonia is a poisonous product of nitrogen metabolism that should be removed from our body. The urea cycle or the ornithine cycle changes the extra ammonia in urea in the mitochondria of the liver cells. The urea form, then enters the blood stream, is filtered with the kidney and is ultimately emitted in the urine.

The overall response to the formation of urea from ammonia is as follows:

2 ammonia + CO2 + 3 ATP —> urea + water + 3 ADP


Amino acid synthesis results result in ammonia. All animals need a way to remove this product. Most aquatic creatures, or ammonotelic organisms, separate ammonia without converting it. Ammonia is toxic, but on immersion from aquatic species, it becomes diluted with water outside the organism. Organizations who can not remove Nitrogen as ammonia easily and safely, can convert it into less toxic substances such as urea or uric acid. The urea cycle is mainly in the liver. The urea produced by the liver is then released into the blood stream where it travels to the kidney and is eventually emitted in the urine. In species with birds and most insects, ammonia is converted to uric acid or its urine salts, which is excreted in solid form.


The entire non-toxic immersion product is converted into urea at the cost of two amino groups, NH 4 + and Aspartate one, and carbon atom from HCO3, four “high energy” phosphate bonds (3 ATP hydrolyzed 2 ADP and An AMP). Conversion from ammonia to urea occurs in five main steps. To enter the cycle, ammonia is necessary for the first time and all four parts of the following four cycle are. To enter the cycle, ammonia is converted into carbamoyl phosphate. There are four enzymatic reactions in the urea cycle: a mitochondrial and three cytosolic.

Steps in Urea Cycle

The urea cycle is a series of five reactions catalyzed by several major enzymes. The first two steps in the cycle are in the mitochondrial matrix and the remaining steps are in cytosol. Thus, urea cycle spreads to two cellular coaches of liver cells.

• In the first stage of the Krebs-Henseleit cycle, ammonia produced in mitochondria is converted into carbamoyl phosphate by the enzyme called carbamoyl phosphate synthesis I. The response can be given as follows:
NH3 + CO2 + 2 ATP → carbamoyl Phosphate + 2 ADP + PI

• In the second stage, the transfer involves transfer of carbamoyl group from carbamoyl phosphate to ornithine from citrulline. This phase is stimulated by the enzyme ornithine transcarbamoylase (OTC). The response is given as follows:
Carbamoyl phosphate + ornithine → citrulline + PI

The citrulline created in this way is left in the cytosol for use in the remaining stages of the cycle.

• The third stage is catalyzed by the enzymes called argininosuccinate synthesis, which uses citrulline and ATP to create citrullyl-AMP intermediate, which responds to the production of argininosuccinate with the amino group from agonnate. This reaction can be given as follows:
Citrulline + ATP + aspartate → argininosuccinate  + AMP + PPI

• Fourth stage involves cleavage of argininosuccinate to make firefighters and arginine. Argininosuccinate lyase enzyme is the reaction catalyst, which can be shown as follows:
argininosuccinate → arginine + fumarate

• In the fifth and final stage of the urea cycle, the arginine is hydrolyzed to make urea and ornithine. It is catalyzed by arginase and can be given as follows:
Arginine → Urea + ornithine

The overall response can be given as follows:

2 NH3 + CO2 + 3 ATP G urea + 2 ADP + AMP + PPI + 2 PI

Importance of Urea Cycle

The main objective of the urea cycle is to eliminate poisonous ammonia from the body. Every day, about 10 to 20 grams of ammonia are removed from the body of a healthy adult. A passive work urea cycle means excess amounts of ammonia in the body, which can lead to hyperammonemia and related illnesses. There may be cycle related disorders due to lack of one or more of the major enzymes that induce various reactions in the urea cycle. In the urea cycle the faults can create vomiting, coma and impulse in newly born children. It is often misidentified as septicemia and is treated with antibiotics in vain. Even 1 mm extra ammonia can cause serious and irreversible damage.

Diagnosis of Urea Cycle Defects

Blood aminogram is regularly used in the diagnosis of urea cycle disorders. The concentration of nitrogen-carrier amino acids, glutamine and alanine in plasma has increased in case of OTC deficiency. In children, high levels of orchic acid in urine can be an indicator of OTC deficiency. In the cases of citrullinemia, increased levels of blood citrulline and argininosuccinate are also seen.

In older children, these disorders can be present in the form of developmental failure, psychiatrist retardation and behavioral abnormalities. Therefore, blood ammonia and urine related orotic surveillance and quantity are important in patients with unclear neurological symptoms.

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